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Two pectic polysaccharides (WRSP-A2b and WRSP-A3a) have been obtained from Radix Sophorae Tonkinensis and comparatively investigated in terms of their physical properties and antioxidant activities. Monosaccharide composition, FT-IR, NMR and enzymatic analyses indicate that both WRSP-A2b (13.6 kDa) and WRSP-A3a (44.6 kDa) consist of homogalacturonan (HG), rhamnogalacturonan I (RG-I) and rhamnogalacturonan II (RG-II) domains, with mass ratios of 0.9:1.8:1 and 2.3:2.9:1, respectively. The RG-I domains were further purified and characterized. Results show that WRSP-A2b contains a highly branched RG-I domain, primarily substituted with α-(1→5)-linked arabinans, whereas WRSP-A3a contains a small branched RG-I domain mainly composed of ß-(1→4)-linked galactan side chains. WRSP-A3a exhibits stronger antioxidant activity in scavenging different radicals than WRSP-A2b, a finding that may be due to its higher content of GalA residues and HG domains. Our results provide useful information for screening natural polysaccharide-based antioxidants from Radix Sophorae Tonkinensis.

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Previous studies by our group demonstrated that radix Sophorae tonkinensis could induce hepatotoxicity. However, it remains unclear which components of this herb may be responsible for its hepatotoxicity. The present study aimed to investigate the hepatic toxicity of treatment with matrine (MT) and oxymatrine (OMT) alone or simultaneously. Furthermore, the current study aimed to identify whether the hepatotoxicity induced by OMT is actually the toxic characterization of its metabolite MT. Hepatotoxicity was evaluated by biochemical and histopathological approaches in subchronic toxicity in mice, as well as via evaluation of cytotoxicity and enzyme leakage in AML12 liver cells. The results indicated that treatment of mice with OMT and MT individually or simultaneously resulted in centrilobular hypertrophy in the liver at doses equivalent to that contained in radix S. tonkinensis at a hepatotoxic dose, suggesting that MT and OMT are likely hepatotoxic components of this herb. OMT-induced hepatotoxicity may be primarily exerted via its metabolite MT in mice. Furthermore, OMT combined with MT was observed to be more toxic compared with OMT or MT alone. These results extend our understanding of the hepatotoxicity of radix S. tonkinensis and its active ingredients.

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Radix Sophorae tonkinensis (S. tonkinensis) is used in Chinese folk medicine to treat sore throats, viral hepatitis, and jaundice. However, little is known about the hepatotoxicity induced by it. This study is to investigate hepatotoxicity induced by radix S. tonkinensis and a potential supplemental biomarker for liver injury through acute toxicity, accumulative toxicity, tolerance test, and sub-chronic toxicity. The contents of cytisine (CYT), matrine (MT), and oxymatrine (OMT) in radix S. tonkinensis extracts were determined simultaneously by the method we developed. In the acute toxicity study, mice were scheduled for single oral gavage at doses of 0, 2.4, 3.2, 4.2, 5.6, 7.5g/kg of radix S. tonkinensis extracts respectively. Another three groups of mice received radix S. tonkinensis extracts orally in single doses of 0, 4.3, 5.6g/kg, while the two groups of the hepatic injury model were induced by intraperitoneal injection with 0.1% and 0.2% carbon tetrachloride (CCl4). Mortality rate, analysis of serum biochemistry, and histopathological examination were used to assess the acute toxicity. In the accumulative toxicity study, mice were treated radix S. tonkinensis extracts orally by the method of dose escalation for 20days respectively. Accumulative toxicity was assessed by mortality rate. In the tolerance test, half of the mice of test group in the accumulative toxicity were administered the dose of 4.3g/kg radix S. tonkinensis extracts, and the rest of the mice in the test group were assigned to receive the dose of 5.6g/kg radix S. tonkinensis extracts. In the sub-chronic toxicity study, mice were treated with daily doses of 0, 0.25, 1.0, 2.5g/kg radix S. tonkinensis extracts for 90days. Assessments of body weights, serum biochemical analysis, and histopathological examination were performed. An enzyme-inhibition assay for butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) of CYT, MT, and OMT was also carried out. The contents of CYT, MT, and OMT in radix S. tonkinensis extracts were 5.63mg/g, 27.63mg/g, and 16.20mg/g respectively. In the acute toxicity study, LD50 of radix S. tonkinensis extracts was 4.3g/kg. No mice were found dead in the accumulative toxicity study. In the acute toxicity and tolerance test, increased ALT, AST, and CHE levels were observed in a dose-response manner, while the severity of histological changes in liver was shown in a dose-dependent mode. In the sub-chronic toxicity, though there was a decline trend of ALT and AST levels found in 0.25g/kg, 1.0g/kg, and 2.5g/kg radix S. tonkinensis extracts as compared to control, which might be related to weight loss, the severity of histopathological changes in the liver and the increased serum CHE level was shown in a dose-response manner. MT, OMT, and CYT showed inhibitory effects on BuChE and AChE in the enzyme-inhibition assay. The results of this study indicate that radix S. tonkinensis should have hepatotoxicity, and increased serum CHE is a potential supplemental biomarker for liver injury.

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Radix Sophorae Tonkinensis (S. tonkinensis) is the processed lateral root of Sophora subprostrata (Leguminosae) that widely distributed over the southwest China. Radix Sophorae Tonkinensis has been widely used as a Chinese medicinal herb for the treatment of disease such as jaundice, inflammation, and aches. Herein, in order to investigate the effects of Radix Sophorae Tonkinensis on the metabolic capacity of rat cytochrome P450 (CYP) enzymes, we employed a cocktail method to evaluate the activities of CYP1A2, CYP2D6, CYP3A4, CYP2C19, CYP2C9 and CYP2B6. The experimental rats were randomly divided into two groups (control group and Radix Sophorae Tonkinensis treated group). The Radix Sophorae Tonkinensis treated group rats were given 5 g/kg Radix Sophorae Tonkinensis by continuous intragastric administration for 14 days. The mixture of six probes (phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and bupropion) was given to rats by intragastric administration. The concentrations of probe drugs in rat plasma were measured by UPLC-MS/MS. The results showed that continuous intragastric administration for 14 days may inhibit the activities of rat CYP450 isoforms CYP2D6, CYP2C19 and CYP2B6. This finding may provide guidance for rational clinical uses of Radix Sophorae Tonkinensis.

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OBJECTIVE: To study the optimal extraction technology of matrine and oxymatrine from Radix Sophorae Tonkinensis. METHODS: The total content of matrine and oxymatrine as the inspection index was determined using high performance liquid chromatography (HPLC). The extraction efficiency of warm immersion extraction, ultrasonic extraction, reflux extraction and accelerated solvent extraction (ASE) was compared. RESULTS: Accelerated solvent extraction was superior to the other three methods. The extraction conditions of accelerated solvent extraction were optimized through single-factor test and orthogonal experimental design. The sequence of influential significance was as follows: extraction times > ethanol concentration > extraction temperature > extraction time. The optimal technology of accelerated solvent extraction was that the ethanol concentration was 40%, extraction temperature was 90°C, the time of extraction was 13 min and the times of extraction was twice. The total content of matrine and oxymatrine from Radix sophorae tonkinensis was (15.5277 ± 0.4316) mg · g-1. CONCLUSION: The experiment has optimized the extraction method and parameters of alkaloid from Radix sophorae tonkinensis, which provides a new method for the extraction of alkaloid from Radix sophorae tonkinensis. Copyright 2012 by the Chinese Pharmaceutical Association.